title: Human receptor for activated protein kinase C1 associates with polyglutamine aggregates and modulates polyglutamine toxicity.
abstract: Formation of SDS-insoluble protein aggregates in affected neurons is a cellular pathological feature of polyglutamine (polyQ) disease. We identified a multi-WD-domain protein, receptor for activated protein kinase C1 (RACK1), as a novel polyQ aggregate component from a Drosophila transgenic polyQ disease model. We showed that WD domains were crucial determinants for the recruitment of RACK1 to polyQ aggregates. Over-expression of the human RACK1 protein suppressed polyQ-induced neurodegeneration in vivo. This is the first report to demonstrate the involvement of WD-domain proteins in polyQ pathogenesis, and the proteomic approach described here can be applied to the investigation of other protein aggregation disorders including Alzheimer's and Parkinson's diseases.
authors.affiliation: Laboratory of Drosophila Research, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China; Molecular Biotechnology Programme, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
authors.forename: Wun
authors.initials: W
authors.lastname: Lam
authors.affiliation: Laboratory of Drosophila Research, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China; Molecular Biotechnology Programme, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
authors.forename: Wing Man
authors.initials: WM
authors.lastname: Chan
authors.affiliation: Laboratory of Drosophila Research, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China; Molecular Biotechnology Programme, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
authors.forename: Tsz Wai
authors.initials: TW
authors.lastname: Lo
authors.affiliation: Laboratory of Drosophila Research, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China; Molecular Biotechnology Programme, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
authors.forename: Azaria Kam Yan
authors.initials: AKY
authors.lastname: Wong
authors.affiliation: Laboratory of Drosophila Research, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China; Molecular Biotechnology Programme, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
authors.forename: Chi Chung
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Laboratory of Drosophila Research, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China; Molecular Biotechnology Programme, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China; Department of Biochemistry (Science), The Chinese University of Hong Kong, Laboratory of Drosophila Research, Molecular Biotechnology Programme, Room 509B, Mong Man Wai Building, Shatin, N.T., Hong Kong SAR, China. Electronic address: hyechan@cuhk.edu.hk.
authors.forename: Ho Yin Edwin
authors.initials: HYE
authors.lastname: Chan
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000235:genetics; D015180:Electrophoresis, Gel, Two-Dimensional; D005561:Formates / Q000737:chemistry; D019204:GTP-Binding Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D020271:Heredodegenerative Disorders, Nervous System / Q000201:enzymology / Q000235:genetics; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D017434:Protein Structure, Tertiary; D040901:Proteomics; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D005561:Formates; D009363:Neoplasm Proteins; D010455:Peptides; C419368:RACK1 protein, human; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; C030544:formic acid; C097188:polyglutamine; D019204:GTP-Binding Proteins